デングウイルス感染における遺伝子型特異的及び遺伝子型交叉性抗体応答のマーモセットモデルを用いた解析

筑波大学 (University of Tsukuba)201

Dengue epidemic in Malaysia: Not a predominantly urban disease anymore

BACKGROUND: Dengue infection has been an important and serious public health concern in Malaysia ever since its first reported case here in 1902. Nevertheless, to our knowledge, no nationwide investigation has been carried out to determine the actual magnitude of dengue endemicity in the Malaysian population. In this study, we describe a cross sectional seroepidemiology study of dengue IgG seroprevalence in the Malaysian adult population. FINDINGS: From 1000 subjects (35-74 years old), 91.6% subjects were found to be dengue seropositive. Age is found to be a significant risk factor associated with dengue seroposivity, where the seroprevalence increased with every 10 year increase in age. Nevertheless, gender and ethnicity did not have an effect. Interestingly, there were similar seroprevalence rates between urban and rural samples, showing that dengue is presently not confined to urban areas in Malaysia. CONCLUSIONS: High dengue IgG seropositivity found in the population is an indication that dengue might be endemic in Malaysia for a long time into the future. Public awareness, proper vector control and vigilant surveillance are critical to keep the infection rates low and to prevent outbreaks

Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys

Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. Preclinical studies in vaccine development usually include parameters such as safety evaluation, induction of viremia and antigenemia, immunogenicity, and vaccine effectiveness. Although mice have been used as a model, non-human primates have an advantage over mice because of their relative similarity to humans in their genetic composition and immune responses. This review compares the viremia kinetics and antibody responses of cynomolgus macaques (Macaca fasicularis), common marmosets (Callithrix jacchus), and tamarins (Saguinus midas and Saguinus labitus) and summarize the perspectives and the usefulness along with challenges in dengue vaccine development

An Overview of Recent Developments in the Application of Antigen Displaying Vaccine Platforms: Hints for Future SARS-CoV-2 VLP Vaccines

Recently, a great effort has been devoted to studying attenuated and subunit vaccine development against SARS-CoV-2 since its outbreak in December 2019. It is known that diverse virus-like particles (VLPs) are extensively employed as carriers to display various antigenic and immunostimulatory cargo modules for vaccine development. Single or multiple antigens or antigenic domains such as the spike or nucleocapsid protein or their variants from SARS-CoV-2 could also be incorporated into VLPs via either a genetic or chemical display approach. Such antigen display platforms would help screen safer and more effective vaccine candidates capable of generating a strong immune response with or without adjuvant. This review aims to provide valuable insights for the future development of SARS-CoV-2 VLP vaccines by summarizing the latest updates and perspectives on the vaccine development of VLP platforms for genetic and chemical displaying antigens from SARS-CoV-2

Hepatitis B and influenza vaccination coverage in healthcare workers, the elderly, and patients with diabetes in Malaysia

Adult immunization remains to be a neglected issue in developing countries including Malaysia. This nationwide study determined the vaccination coverage of hepatitis B and influenza among Malaysia’s healthcare workers (HCWs), the elderly (aged 60 y and above) and patients with diabetes, who are the participants of The Malaysia Cohort Program. The participants were categorized based on their occupation, age and medical history. Self-reported questionnaire was used to assess the participant’s hepatitis B and influenza vaccination status. A Chi-square test and logistic regression analyses were performed to determine the risk factors associated with vaccination behavior. The hepatitis B vaccination coverage for healthcare workers, elderly, and patients with diabetes were 34.6%, 10.1% and 9.8%, respectively. The influenza vaccination coverage rates for healthcare workers, the elderly and patients with diabetes were 26.3%, 5.5% and 6.4%, respectively. The Chinese were more likely to be vaccinated against hepatitis B, while Malay was more likely to be vaccinated against influenza. Individuals with higher education and living in urban areas were more likely vaccinated than those with low education levels and who lived in rural areas. The low vaccination coverage for healthcare workers was alarming because hepatitis B and influenza were subsidized for the healthcare workers. The hepatitis B and influenza vaccination coverage among healthcare workers, elderly and patients with diabetes in Malaysia were low. Specific interventions such as educational and awareness programs should be conducted to increase the vaccination rate among adults, especially those at high risk

Genotype-specific and cross-reactive neutralizing antibodies induced by dengue virus infection: detection of antibodies with different levels of neutralizing activities against homologous and heterologous genotypes of dengue virus type 2 in common marmosets (Callithrix jacchus)

Abstract Background A vaccine against all four dengue virus (DENV) serotypes includes the formulation of one genotype of each serotype. Although genetic similarities among genotypes within a serotype are higher as compared to those among serotypes, differences in the immunogenicity of the included genotypes would be a critical issue in maximizing successful dengue vaccine development. Thus, we determined the neutralizing antibody responses against three genotypes of dengue virus serotype 2 (DENV-2), namely Cosmopolitan, Asian I, and Asian/American, after primary and secondary inoculation with DENV-2 in a dengue animal model, the common marmoset (Callithrix jacchus). Methods A total of fifty-four plasma samples were obtained from thirty-four marmosets that were inoculated with clinically-isolated DENV strains or DENV candidate vaccines, were used in this study. Plasma samples were obtained from marmosets after primary inoculation with DENV-2 infection, secondary inoculation with homologous or heterologous genotypes, and tertiary inoculation with heterologous DENV. Neutralizing antibody titers against DENV-2 (Cosmopolitan, Asian I, and Asian/American genotypes) and DENV-1 were determined using a conventional plaque reduction neutralization assay. Results In marmosets that were inoculated with the Cosmopolitan genotype in primary infection, neutralizing antibody neutralized 3 genotypes, and the titers to Asian I genotype were significantly higher than those to homologous Cosmopolitan genotype. After secondary DENV-2 infection with heterologous genotype (Asian I in primary and Asian/American in secondary), neutralizing antibody titers to Asian/American genotype was significantly higher than those against Cosmopolitan and Asian I genotypes. Following tertiary infection with DENV-1 following DENV-2 Asian I and Cosmopolitan genotypes, neutralizing antibody titers to Asian/American were also significantly higher than those against Cosmopolitan and Asian I genotypes. Conclusion The present study demonstrated that different levels of neutralizing antibodies were induced against variable DENV-2 genotypes after primary, secondary and tertiary infections, and that neutralizing antibody titers to some heterologous genotypes were higher than those to homologous genotypes within a serotype. The results indicate that heterogeneity and homogeneity of infecting genotypes influence the levels and cross-reactivity of neutralizing antibodies induced in following infections. The results also suggest that certain genotypes may possess advantage in terms of breakthrough infections against vaccination